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1.
J Biomater Sci Polym Ed ; 31(2): 244-260, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31626738

RESUMO

Drug-eluting stents have been widely used in the clinic because of their impressive ability to reduce restenosis. However, the conventional biodegradable polymers used for drug-loaded coatings undergo bulk erosion, which can induce internal catalysis, resulting in a high local acidity during the degradation process and unfavorable side-effects. Herein, poly(1,3-trimethylene carbonate), a surface eroding biodegradable polymer, was chosen as a drug-loaded coating for cardiovascular stents. We modified both sides of the stent to simultaneously promote re-endothelialization at the inner layer and reduce restenosis at the outer layer, using a titanium oxide (Ti-O) film as the inner layer and a Ti-O film/drug coating as the outer layer. In vitro and in vivo results indicated that the Ti-O film accelerated endothelial cell growth and re-endothelialization, and the drug coating inhibited platelet adhesion, activation, and aggregation, smooth muscle cell proliferation, and significantly reduced neointimal hyperplasia. Therefore, this novel stent may have potential as a cardiovascular stent to treat patients with coronary artery stenosis.

2.
J Autoimmun ; 106: 102349, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31629629

RESUMO

BACKGROUND: Genome-wide association studies have identified over 120 risk loci for psoriasis. However, most of the variations are located in non-coding region with high frequency and small effect size. Pathogenetic variants are rarely reported except HLA-C*0602 with the odds ratio being approximately 4.0 in Chinese population. Although rare variations still account for a small proportion of phenotypic variances in complex diseases, their effect on phenotypes is large. Recently, more and more studies focus on the low-frequency functional variants and have achieved a certain amount of success. METHOD: Whole genome sequencing and sanger sequencing was performed on 8 MZ twin pairs discordant for psoriasis to scan and verified the de novo mutations (DNMs). Additionally, 665 individuals with about 20 years' medical history versus 2054 healthy controls and two published large population studies which had about 8 years' medical history (including 10,727 cases versus 10,582 controls) were applied to validate the enrichment of rare damaging mutations in two DNMs genes. Besides, to verify the pathogenicity of candidate DNM in C3, RNA-sequencing for CD4+, CD8+ T cells of twins and lesion, non-lesion skin of psoriasis patients were carried out. Meanwhile, the enzyme-linked immunosorbent assay kit was used to detect the level of C3, C3b in the supernatant of peripheral blood. RESULT: A total of 27 DNMs between co-twins were identified. We found six of eight twins carry HLA-C∗0602 allele which have large effects on psoriasis. And it is interesting that a missense mutation in SPRED1 and a splice region mutation in C3 are found in the psoriasis individuals in the other two MZ twin pairs without carrying HLA-C*0602 allele. In the replication stage, we found 2 loss-of-function (LOF) variants of C3 only in 665 cases with about 20 years' medical history and gene-wise analysis in 665 cases and 2054 controls showed that the rare missense mutations in C3 were enriched in cases (OR = 1.91, P = 0.0028). We further scanned the LOF mutations of C3 in two published studies (about 8 years' medical history), and found one LOF mutation in the case without carrying HLA-C*0602. In the individual with DNM in C3, RNA sequencing showed the expression level of C3 in skin was significant higher than healthy samples in public database (TPM fold change = 1.40, P = 0.000181) and ELISA showed protein C3 in peripheral blood was higher (~2.2-fold difference) than the other samples of twins without DNM in C3. CONCLUSION: To the best of our knowledge, this is the first report that DNM in C3 is the likely pathological mutations, and it provided a better understanding of the genetic etiology of psoriasis and additional treatments for this disease.

3.
Mol Genet Genomic Med ; 8(2): e1098, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31858748

RESUMO

BACKGROUND: Psoriasis is a chronic inflammatory disorder of the skin, and genetic factors are reported to be involved in the disease pathogenesis. Many studies have named psoriasis candidate genes. OBJECTIVE: In this study, we determined the mutation frequency of 7 variable genes in 1,027 psoriatic patients and investigated its possible mechanism associated with psoriasis. METHOD: A total of 7 variable genes from 1,027 psoriatic patients were amplified and sequenced using the Sanger method. The mutation frequency was compared to that of non-psoriatic individuals in Asia using information from databases. RESULTS: Among the 7 investigated genes, the mutation frequency of ACOT12 (c.80A>G, 9.98% vs. 5.85%, p < .05) and CT62 (c.476C>T,15.8% vs. 9.93%, p < .05) was found to be significantly higher than among non-psoriatic Asian individuals. The mutation frequencies of CASZ1(c.599T>G), SPRED1(c.155A>G), and ACOT12 (c.80A>G) differed significantly between the groups organized by medical history, PASI, and family history. SPRED1 gene variants (17.25% vs. 7.78%, p < .01) showed a stronger association with the family history group at the onset of psoriasis than with the no family history group. CONCLUSIONS: Our results provide a comprehensive correlation analysis of susceptibility genes in psoriasis patients. Clinical characteristics of patients play important roles in the development of psoriatic skin.

4.
J Biomed Nanotechnol ; 15(12): 2393-2400, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748019

RESUMO

Hepatitis B virus (HBV) is closely related to occurrence and development of viral hepatitis. A mutation of 1896nt locus in its pre-C region can promote replication of HBV DNA and improve stability of pre-genome RNA structure, and can even help HBV evade immune clearance. In this study, magnetic beads-probe (MBs@probe) method, combined with single base extension (SBE) technology, was developed for in-situ mutation detection of HBV pre-C region 1896nt locus. Before successfully completing the genotyping of 165 HBV samples, the crucial reaction conditions were first optimized, such as SBE temperature, MBs size and amount, and probe concentration on the surface of MBs. Experimental results showed that these conditions had significant effects on MBs@probe in-situ mutation detection. Comprehensive considerations, such as 58 °C of SBE temperature, high fluorescence intensity and signal-to-noise ratios (SNRs) were obtained when MBs@probe complex was made by 100 µg of 300 nm-MBs and 3.0 µM of probes in the system. Finally, 1896nt locus mutation in pre-C region of 165 HBV samples was successfully genotyped, among which 71 HBV samples were wild types and the remaining 94 samples were mutant types. Meanwhile, 14 randomly chosen samples were taken to further analyze fluorescence intensity and SNRs respectively, and sequencing results for the first two samples were consistent with results from the MBs@probe in-situ mutation detection method. Compared with two-color fluorescence hybridization (TCFH) genotyping technology, this method generally improves the SNRs to more than 10 (which is more than 2-fold), has higher reliability and is more suitable to detect SNPs for known sites.


Assuntos
Vírus da Hepatite B , Herpesvirus Cercopitecino 1 , Polimorfismo de Nucleotídeo Único , DNA Viral , Genótipo , Hepatite B , Humanos , Mutação , Reprodutibilidade dos Testes
5.
Oncol Lett ; 18(5): 5459-5467, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612054

RESUMO

Cholangiocarcinoma (CCA) is a biliary epithelial tumor with poor prognosis. As the key genes and signaling pathways underlying the disease have not been fully elucidated, the aim of the present study was to improve the understanding of the molecular mechanisms associated with CCA. The microarray datasets GSE26566 and GSE89749 were downloaded from the Gene Expression Omnibus and differentially expressed genes (DEGs) between CCA and normal bile duct samples were identified. Gene and pathway enrichment analyses were performed, and a protein-protein interaction network was constructed and analyzed. A total of 159 DEGs and 10 hub genes were identified. The functions and pathways of the DEGs were mainly enriched in 'heparin binding', 'serine-type endopeptidase activity', 'calcium ion binding', 'pancreatic secretion', 'fat digestion and absorption' and 'protein digestion and absorption'. Survival analysis revealed that the upregulated expression of carboxypeptidase B1 and Kruppel like factor 4 was significantly associated with lower overall survival rate. In summary, the present study identified DEGs and hub genes associated with CCA, which may serve as potential diagnostic and therapeutic targets for the disease.

6.
Biotechnol Lett ; 41(12): 1361-1371, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31631231

RESUMO

OBJECTIVE: Although several methods have been reported and used for in vitro T cell amplification, there are no consistent reports on the optimal stimulation conditions and the characterization of these stimulated T cells. The current study aimed to determine the optimal conditions for efficient T cell amplification by two commonly used methods involving CD3/CD28 antibody and phytohemagglutinin (PHA), respectively. RESULTS: Orthogonal design and CCK8 assay showed that 5 µg/mL CD3, 5 µg/mL CD28, and 100 ng/mL IL2 for the first method and 50 µg/mL PHA for the second method was optimal for T cell stimulation. Flow cytometry demonstrated that the percentage of CD8+ in the stimulated groups significantly increased, while the percentage of CD4+/CD8+ was significantly decreased compared with the unstimulated group. The percentage of CD4+ showed no significant difference among the three groups. Notably, there was no significant difference between the two stimulated groups. In addition, the percentage of apoptotic cells was significantly increased in the stimulated groups compared with the unstimulated group, but showed no remarkable difference between the PHA and CD3/CD28 stimulation groups. Glycolysis analysis showed that the glycolytic capacity and glycolytic reserve were both significantly increased in the PHA and CD3/CD28 groups compared with the unstimulated group, with no significant difference noted between the stimulated groups. CONCLUSIONS: Although both stimulation methods showed similar efficacies, we suggest the PHA method might be better considering its easy application and cost-effective nature.

7.
Ann Clin Lab Sci ; 49(5): 671-674, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31611213

RESUMO

More than 100 cases harboring both myeloproliferative neoplasms (MPN) and chronic lymphocytic leukaemia (CLL) have been reported, suggesting that the two diseases can coexist in one patient. However, the mechanism by which this phenomenon is caused remains unclear. In this study, one patient with polycythemia vera (PV) and CLL is examined. Identifications of the JAK2V617F and P53H179L/ P53R209fs mutations were obtained via targeted next generation sequencing. Furthermore, B lymphocytes and neutrophils were separated from peripheral blood. This led to the discovery that JAK2V617F occurs in neutrophil's compartment, with P53 mutations emerging in B lymphocytes. These results indicate that PV and CLL are independent clonal diseases in this case, rather than phenotypes derived from one clone.

8.
Anal Chem ; 91(20): 13290-13296, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31508942

RESUMO

The application of different sensing principles in microfluidic devices opens up further possibilities for the development of point-of-care testing (POCT). Herein, the photothermal sensing principle is introduced in microfluidic paper-based analytical devices (µPADs) to develop a photothermal microfluidic sensing platform using near-infrared (NIR) laser-driven multiplexed dual-mode visual quantitative readout. Prussian blue (PB) as the analyte-associated photothermal agent was in situ synthesized in thermoresponsive poly(N-isopropylacrylamide) hydrogels to serve as the on-chip photothermal sensing element. The NIR laser-driven photothermal effect of PB triggered not only on-chip dose-dependent heat generation but also phase transition-induced dye release from the hydrogels, simultaneously enabling both thermal image- and distance-based dual-mode visual quantitative readout of the analyte concentration in a multiplexed manner. Both the on-chip temperature elevation value of the hydrogels and the traveling distance of released dye solutions were proportional to the concentration of PB. With the detection of silver ions in environmental water as a proof-of-concept study, the photothermal µPAD can detect silver ions at a concentration as low as 0.25 µM with high selectivity and satisfactory accuracy. The photothermal microfluidic sensing platform holds great potential for POCT with promising integratability and broad applicability, owing to the combination of synergistic advantages of the photothermal sensing principle, µPADs, and photothermally responsive hydrogels.

9.
J Mater Chem B ; 7(36): 5490-5501, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31418434

RESUMO

Pluronic F127 diacrylate (F127DA) nano-micelle crosslinked methacrylated hyaluronic acid (MeHA) hydrogels (NMgels) with strong compressive properties have been demonstrated in our previous study. The current study further focuses on how the F127DA micelles and long-term swelling affect the mechanical performance of hydrogels from the view of in vitro/in vivo applications. Co-contributions of the F127DA micelles and MeHA to the compression performance are first investigated through mechanical analysis and cyclic loading/unloading tests before and after swelling. The optimized NMgel with F127DA micelles of 15 wt% and MeHA of 1.5 wt% (F15H1.5) exhibits a low swelling ratio and a well-maintained network in pH = 7.4 phosphate buffered saline. The abundant hydration significantly affects the initial mechanical properties of the hydrogels. After swelling, the compressive strength, modulus and fracture energy of F15H1.5 NMgel decrease from ∼3.44 MPa, ∼312 kPa and ∼407.5 kJ m-3 to 0.59 MPa, ∼55 kPa, and ∼81.8 kJ m-3, respectively. The energy dissipation of the first loading-unloading cycle dramatically decreases from ∼21.5 kJ m-3 to ∼6.0 kJ m-3 as well. Nevertheless, the gel still retains excellent stiffness, toughness and self-recovery due to the dense and strong micelle linkages. In vivo studies show that the implantation of F15H1.5 hydrogel in thyroid cartilage defects of rabbit larynx effectively promotes the regeneration of cartilage after 8 weeks. These results indicate that the stiff NMgel is a promising cartilage tissue engineering scaffold for the regeneration of cartilage in vivo.

10.
Cancer Med ; 8(11): 5254-5263, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31294534

RESUMO

MPLW515K or W515L mutation plays an important role in the pathogenesis of myeloproliferative neoplasms (MPNs) through signaling molecules of the cytokine receptor axis. Besides MPLW515K or W515L, more than 30 atypical MPL mutations have been reported in patients who are negative for JAK2V617F, MPLW515K/L, and CALR mutations. Here, we aimed to identify the disease-causing mutations in the triple-negative case of ET. We described two MPL mutations in patients diagnosed with ET by target sequencing the hotspot mutation region of MPL gene. The MPLA497-L498ins4 is an insertion mutation detected recurrently in ET patients, and the MPLW515RQ516E is a novel double-point mutation found in an ET patient. Functional studies of MPLA497-L498ins4 and MPLW515RQ516E revealed that they are gain-of-function mutations. Mutants of MPLA497-L498ins4 and MPLW515RQ516E promoted autonomous proliferation on Ba/F3 cells in the absence of IL-3. Autonomous activation of TPO-R without ligand TPO was observed in MPLA497-L498ins4 and MPLW515RQ516E mutants. Lower percentage of cells in G1 phase and higher percentage of cells in S phase of two atypical MPL mutants were detected after culturing without any cytokines. These two atypical MPL mutations also presented increase in phosphorylation of signaling proteins including JAK2/STAT, PI3K/AKT, and MAPK/RAS. In summary, the MPLA497-L498ins4 and MPLW515RQ516E are gain-of-function mutations which may be novel driving factors participating in the pathogenesis of triple-negative MPN.

11.
Colloids Surf B Biointerfaces ; 179: 208-217, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30959233

RESUMO

Polyurethane is a good matrix material with wide application prospects in tissue engineering because of its adjustable and mechanical properties. A novel biodegradable crosslinked poly(ester urethane) (CPU) with flexible poly(caprolactone) (PCL) and hydrophilic poly(ethylene glycol) (PEG) components has been synthesized using a ferric iron catalyst in our laboratory. In the present study, to promote the interaction between the CPU material and cells, the material was superficially modified by silk fibroin (SF) grafting using an aminolysis and glutaraldehyde crosslinking method to achieve a biocompatible material, CPU-SF. Considering the esophageal-specific architecture, three types of scaffolds were fabricated. S1 was a CPU-SF channel (200 µm in diameter and 30 µm in depth with 30 µm of wall thickness) to support muscle regeneration; S2 was the decellularized matrix of the esophageal mucosa/submucosa obtained by enzyme treatment; and S3 was a combination of S1 and S2, aiming to promote esophageal regeneration with histological structure and function. The biological properties and functions of the materials and scaffolds were investigated by qualitative and quantitative analyses using scanning electron microscopy, immunofluorescence staining, cell adhesion and proliferation measurements, and western blotting technology. The results showed that esophageal smooth muscle cells (SMCs) and epithelial cells (ECs) were very well supported by the scaffolds. In particular, SMCs exhibited guided directional growth and ECs infiltrated the acellular mucosa with retained biological functions when co-cultured on the composite scaffold S3. These findings suggest that the composite bionic scaffold will be a good alternative for esophageal replacement.


Assuntos
Biônica , Esôfago/fisiologia , Poliésteres/farmacologia , Poliuretanos/farmacologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Linhagem Celular , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Membrana Mucosa/ultraestrutura , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Coelhos
12.
Int J Nanomedicine ; 14: 1359-1383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863066

RESUMO

Slp forms a crystalline array of proteins on the outermost envelope of bacteria and archaea with a molecular weight of 40-200 kDa. Slp can self-assemble on the surface of liposomes in a proper environment via electrostatic interactions, which could be employed to functionalize liposomes by forming Slp-coated liposomes for various applications. Among the molecular characteristics, the stability, adhesion, and immobilization of biomacromolecules are regarded as the most meaningful. Compared to plain liposomes, Slp-coated liposomes show excellent physicochemical and biological stabilities. Recently, Slp-coated liposomes were shown to specifically adhere to the gastrointestinal tract, which was attributed to the "ligand-receptor interaction" effect. Furthermore, Slp as a "bridge" can immobilize functional biomacromol-ecules on the surface of liposomes via protein fusion technology or intermolecular forces, endowing liposomes with beneficial functions. In view of these favorable features, Slp-coated liposomes are highly likely to be an ideal platform for drug delivery and biomedical uses. This review aims to provide a general framework for the structure and characteristics of Slp and the interactions between Slp and liposomes, to highlight the unique properties and drug delivery as well as the biomedical applications of the Slp-coated liposomes, and to discuss the ongoing challenges and perspectives.


Assuntos
Tecnologia Biomédica/métodos , Sistemas de Liberação de Medicamentos , Lipossomos/química , Glicoproteínas de Membrana/química , Lipossomos/ultraestrutura , Eletricidade Estática
13.
Stem Cell Res Ther ; 10(1): 54, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760317

RESUMO

BACKGROUND: Psoriasis is a chronic and systemic, immune-mediated, inflammatory disease. Mesenchymal stem cells have effects on the inflammatory microenvironment, including regulating the proliferation, differentiation, recruitment, and migration of immunocytes. METHODS: To investigate whether dermal mesenchymal stem cells (DMSCs) may act on migration of immunocytes in psoriasis patients, 22 patients with psoriasis and 22 matching healthy controls (age and sex in this study) were recruited. Seven migration-associated genes including chemokine like receptor-1 (CMKLR-1), collagen type VIII alpha1 (COL8A-1), neuropilin and tolloid-like 2 (NETO-2), nik-related kinase (NRK), secreted frizzled-related protein (SFRP), sulfate 6-O-endosulfatase 2 (SULF-2), and synaptotagmin-like protein 2 (SYTL-2) were analyzed by quantitative real-time reverse transcription PCR and western blot. Peripheral blood-derived mononuclear cells (PBMCs) migration to MSCs was measured using a Thanswell chamber system. RESULTS: We observed the upregulation of CMKLR-1, COL8A-1, NETO-2, NRK, SYTL-2, and SULF-2 in dermal mesenchymal stem cells derived from patients with psoriasis at both mRNA and protein level, however, a significant downregulation of SFRP-2 between two groups. By contrast, there were no significant between-group differences at the mRNA and protein expression level of NETO-2 and SULF-2. The migration assay showed that in vitro the normal PBMC migration to psoriatic DMSC group was a 6.3 ± 0.7-fold increase compared with the control group. CONCLUSIONS: The results may suggest a potential pathogenetic involvement of DMSCs on migration of monocytes in psoriasis. Immune responses are regulated at the level of DMSCs, which probably represent the cells primarily involved in the "psoriatic march."

14.
Biomolecules ; 9(2)2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30781704

RESUMO

Drug-eluting stents (DES) have been widely applied for saving the life of patients with coronary artery diseases (CADs). However, conventional polymers such as polylactic acid (PLA) and poly (lactic-co-glycolic acid) (PLGA), which are widely applied for drug-eluting stents studies, have serious bulk erosion problems, like high local acidity and poor mechanical properties. Instead, we chose surface erosion polymer poly (1, 3-trimethylene carbonate) (PTMC) as a drug carrier in this study. Here, we fabricated and characterized a novel durable-polymer drug-eluting 316 L stainless steel (SS) stent, in which the inner surface was coated with a Ti⁻O film using the magnetron sputtering method to promote the growth of endothelial cells (ECs). On the outer layer of the stent, first, a Ti⁻O film was deposited and, then, on top of it a rapamycin-loaded PTMC coat was deposited using the ultrasonic atomization spray method. This dual coating inhibited the migration and expansion of smooth muscle cells (SMCs). The drug coating also inhibited the adhesion/activation of platelets. In tests on dogs, it was found the novel stent promoted re-endothelialization and reduced restenosis, in contrast to the plain SS stent. Thus, the novel stent may have promise for use in treating patients with CAD.


Assuntos
Anticoagulantes/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Stents Farmacológicos , Animais , Anticoagulantes/química , Coagulação Sanguínea/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Cães , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Teste de Materiais , Miócitos de Músculo Liso/efeitos dos fármacos , Tamanho da Partícula , Ativação Plaquetária/efeitos dos fármacos , Propriedades de Superfície
16.
Cell Tissue Bank ; 19(3): 277-285, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29159500

RESUMO

Mesenchymal stem cells (MSCs) are used for tissue regeneration in several pathological conditions, including autoimmune diseases. However, the optimal sources and culture requirements for these cells are still under investigation. Here, we compared mRNA expression in dermal MSCs (DMSCs) at passage (P) 3 and P5 to provide a reference for future studies related to DMSCs expansion. In normal DMSCs, the expression of three of eight genes associated with basic cellular activity were different at P5 compared to that at P3: PLCB4 and SYTL2 were upregulated by 4.30- and 6.42-fold, respectively (P < 0.05), whereas SATB2 was downregulated by 39.25-fold (P < 0.05). At the same time, genes associated with proliferation, differentiation, inflammation, and apoptosis were expressed at similar levels at P3 and P5 (P > 0.05). In contrast, in DMSCs isolated from psoriatic patients we observed differential expression of three inflammation-associated genes at P5 compared to P3; thus IL6, IL8, and CXCL6 mRNA levels were upregulated by 16.02-, 31.15-, and 15.04-fold, respectively. Our results indicate that normal and psoriatic DMSCs showed different expression patterns for genes related to inflammation and basic cell activity at P3 and P5, whereas those for genes linked to proliferation, differentiation, and apoptosis were mostly similar.


Assuntos
Apoptose , Diferenciação Celular , Proliferação de Células , Derme/citologia , Células-Tronco Mesenquimais/citologia , RNA Mensageiro/genética , Adulto , Técnicas de Cultura de Células/métodos , Células Cultivadas , Derme/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo
17.
J Dermatol Sci ; 86(3): 181-186, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27894778

RESUMO

Psoriasis is a complex chronic relapsing inflammatory disease. Although the exact mechanism remains unknown, it is commonly accepted that the development of psoriasis is a result of multi-system interactions among the epidermis, dermis, blood vessels, immune system, neuroendocrine system, metabolic system, and hematopoietic system. Many cell types have been confirmed to participate in the pathogenesis of psoriasis. Here, we review the stem cell abnormalities related to psoriasis that have been investigated recently.


Assuntos
Células-Tronco Hematopoéticas/patologia , Células-Tronco Mesenquimais/patologia , Psoríase/patologia , Pele/patologia , Proteínas Angiogênicas/metabolismo , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Fenótipo , Psoríase/imunologia , Psoríase/metabolismo , Transdução de Sinais , Pele/imunologia , Pele/metabolismo
18.
Colloids Surf B Biointerfaces ; 145: 72-78, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27137805

RESUMO

The migration dynamics of cells plays a key role in tissue engineering and regenerative medicine. Previous studies mostly focus on regulating stem cell fate and phenotype by biophysical cues. In contrast, less is known about how the geometric cues mediate the migration dynamics of cells. Here, we fabricate graphene oxide (GO) microstripes on cell non-adhesive PEG substrate by using micromolding in capillary (MIMIC) method. Such micropatterns with alternating cell adhesion and cell resistance enable an effective control of selective adhesion and migration of single cells. The sharp contrast in cell adhesion minimizes the invasion of cells into the PEG patterns, and thereby strongly confines the cells on GO microstripes. As a result, the cells are forced to adapt highly polarized, elongated, and oriented geometry to fit the patterns. A series of pattern widths have been fabricated to modulate the extent of cell deformation and polarization. Under strong confinement, the cytoskeleton contractility, intracellular traction, and actin filament elongation are highly promoted, which result in enhanced cell migration along the patterns. This work provides an important insight into developing combinatorial graphene-based patterns for the control of cell migration dynamics, which is of great significance for tissue engineering and regenerative medicine.


Assuntos
Grafite/química , Óxidos/química , Movimento Celular/fisiologia , Citoesqueleto/metabolismo , Humanos , Osteoblastos/citologia , Osteoblastos/metabolismo
19.
Int J Dermatol ; 55(5): e280-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26748901

RESUMO

BACKGROUND: Recent experimental studies revealed that angiogenesis and lymphangiogenesis are closely related to psoriasis. Our microarray analysis suggested that the pro-angiogenic genes platelet endothelial cell adhesion molecule-1 (PECAM1), facio-genital dysplasia-5 (FGD5), prostaglandin-endoperoxide synthase-1 (PTGS1), melanoma cell adhesion molecule (MCAM), vasohibin-2 (VASH2), and stabilin-1 (STAB1) are differentially expressed in dermal mesenchymal stem cells in psoriasis. OBJECTIVES: The aim of this study was to investigate the mRNA and protein expression of PECAM1, FGD5, PTGS1, MCAM, VASH2, and STAB1 for angiogenesis and the possible mechanisms in psoriasis. METHODS: We studied 12 patients with plaque psoriasis and 14 healthy controls matched for age and sex. Dermal mesenchymal stem cells were expanded, passaged, and identified by cellular morphology, immunophenotyping, and multipotential differentiation. The mRNA and protein expression of the above-mentioned six genes were confirmed by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting. RESULTS: The significantly decreased expression of PECAM1, PTGS1, FGD5, and MCAM at both mRNA and protein level (except VASH2 and STAB1) were demonstrated in mesenchymal stem cells from psoriatic skin lesions compared with non-lesional from healthy controls. CONCLUSIONS: We provide the first report that pro-angiogenic genes PECAM1, PTGS1, FGD5, and MCAM rather than VASH2 and STAB1 may be play a vital role in pathological dermal angiogenesis disorders of psoriasis. Therefore, anti-angiogenesis is attractive and offers future potential for application in patients with psoriasis.


Assuntos
Expressão Gênica , Células-Tronco Mesenquimais , Neovascularização Patológica/genética , Psoríase/genética , RNA Mensageiro/metabolismo , Adulto , Proteínas Angiogênicas/genética , Proteínas Angiogênicas/metabolismo , Antígeno CD146/genética , Antígeno CD146/metabolismo , Estudos de Casos e Controles , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Diferenciação Celular , Células Cultivadas , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , Feminino , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Imunofenotipagem , Masculino , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Psoríase/metabolismo , Receptores de Retorno de Linfócitos/genética , Receptores de Retorno de Linfócitos/metabolismo , Índice de Gravidade de Doença , Adulto Jovem
20.
Biotechnol Lett ; 38(1): 33-41, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26463369

RESUMO

OBJECTIVE: We characterized mRNA expression profiles in normal and psoriatic human dermal mesenchymal stem cells (DMSCs) to provide a reference for future investigation of differential gene expression in DMSCs. RESULTS: Microarray and RNA sequencing (RNA-Seq) analyses both identified 23 differentially expressed genes using both platforms. The results showed comparable upregulation or downregulation for 14/23 genes using either platform and a 100 % coincidence rate was found by real-time PCR. For all of the differentially expressed genes that were verified by real-time PCR, the coincidence rate for RNA-Seq and real-time PCR was significantly higher than that for microarray analysis and real-time PCR (83.3 vs. 37.5 %, P < 0.0001). Furthermore, RNA-Seq revealed the presence of over 2300 novel transcription tags. CONCLUSION: Relative to microarray analysis, RNA-Seq is more accurate in identifying differentially expressed genes in DMSCs.


Assuntos
Perfilação da Expressão Gênica/métodos , Células-Tronco Mesenquimais/citologia , Psoríase/genética , Análise de Sequência de RNA/métodos , Adulto , Células Cultivadas , China , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Células-Tronco Mesenquimais/patologia , Psoríase/patologia
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